过氧化物酶体增殖物激活受体γ激动剂对肝星状细胞增殖的影响

Effects of peroxisome proliferator-activated receptor agonists on the proliferation of hepatic stellate cells

目的观察过氧化物酶体增殖物激活受体γ(PPARγ)激动剂对肝星状细胞增殖的影响,探讨其抗肝纤维化的可能作用机制。方法利用胶原酶原位灌注梯密度离心方法分离大鼠肝星状细胞(HSC),利用噻唑蓝(MTT)比色法、流式细胞技术检测曲格列酮、15-脱氧-前列腺素J2 (15-d-PGJ_2)对HSC增殖及细胞周期的作用。结果MTT检测表明曲格列酮、15-d-PGJ_2在5～100μmol/L浓度范围内可显著抑制HSC的增殖,与对照组比较P<0.01;流式细胞检测表明25、50μmol/L的曲格列酮可显著降低HSC S期细胞数量,降低细胞增殖指数,与对照组比较,差异有统计学意义(P<0.05)。结论PPARγ激动剂通过影响HSC的增殖而发挥其抗肝纤维化作用。

Objective To study the effects of peroxisome proliferator-activated receptor v （PPARγ） agonists on the proliferation of hepatic stellate cells （HSC） and the possible mechanisms to inhibit liver fibrosis. Methods HSC were isolated from normal rat liver tissue. MTT colorimetry and flow cytometry were used to study the effects of troglitazone and 15-deoxy-prostaglandin J2 （ 15-d-PGJ2 ） on the proliferation and cell cycles of HSC. Results The MTT analysis results showed that both troglitazone and 15-d-PGJ2 could significantly inhibit HSC proliferation in a range of 5 and 100 γmol/L in a dose-dependent manner as compared with the control group （ P 〈 0.01 ）. Flow cytometry revealed that cells in S phase and the index of cell proliferation were markedly decreased after treated with 25 and 50 γmol/L troglitazone as compared with the control group （ P 〈 0.05）. Conclusion PPARγ agonists exert the anti-fibrosis action by inhibiting the proliferation of HSC.